This study investigated classical scrapie susceptibility in four native Italian sheep breeds (Lamon, Brogna, Alpagota, Foza) through PrP genotyping. The investigation revealed that the majority of animals overall showed moderate to high susceptibility to classical scrapie. The Lamon and Brogna breeds exhibited the highest frequency of the highly susceptible VRQ allele (38.1% and 19.3%, respectively), while the Alpagota and Foza had a high frequency of the ARQ allele (85% and 64%, respectively), also considered to confer susceptibility. The Foza breed showed a significantly high frequency (P<0.01) of the rare ARK allele (9.7%); a similar frequency has never been described before in the literature. This study stresses the importance of genotyping native sheep breeds both to better organize conservation schemes and to assess the risk of contracting classical scrapie. Additionally, the investigated native breeds revealed some characteristics that could be interesting for research purposes. These sheep could in fact be used to investigate the susceptibility of the ARK allele to classical scrapie, but also to determine whether its relatively high frequency is indicative that the origin of the Foza breed differs from the other Venetian sheep breeds.